Refinement Database

Database on Refinement of Housing, Husbandry, Care, and Use of Animals in Research

This database, created in 2000, is updated every four months with newly published scientific articles, books, and other publications related to improving or safeguarding the welfare of animals used in research.

Tips for using the database:

  • This landing page displays all of the publications in the database.
  • Use the drop-down menus to filter these publications by Animal Type, Setting, and/or Topic.
  • Clicking on a parent category (e.g., Rodent) will include publications relating to all the items in that category (e.g., Chinchilla, Gerbil, Guinea Pig, etc.).
  • You may also add a keyword to further narrow your search.
  • Please note that at this time, only publications dated 2010 or later (with some exceptions) can be filtered by Animal Type and Topic, and only publications dated 2020 or later (with some exceptions) can be filtered by Setting. Most publications older than 2010 can only be searched by keyword. 
Weaver, H. L., Carbaugh, C. M., Madejczyk, M. S. et al. 2024. Comparison of tricaine methanesulfonate (MS-222) and alfaxalone anesthesia in zebrafish (Danio rerio). JAALAS 63(1), 74–80.

The research use of zebrafish has risen exponentially over the past decade while anesthetic options have remained largely unchanged.6 ricaine methanesulfonate (MS-222) is widely accepted as an anesthetic for routine husbandry procedures, however it has...

Farag, A., Mandour, A. S., Hendawy, H. et al. 2023. A review on experimental surgical models and anesthetic protocols of heart failure in rats. Frontiers in Veterinary Science 10, 1103229.

Heart failure (HF) is a serious health and economic burden worldwide, and its prevalence is continuously increasing. Current medications effectively moderate the progression of symptoms, and there is a need for novel preventative and reparative...

Mauthe von Degerfeld, M., Serpieri, M., Bonaffini, G. et al. 2023. Intranasal atomization of ketamine, medetomidine and butorphanol in pet rabbits using a mucosal atomization device. Animals 13(13), 2076.

A non-invasive method of drug delivery, intranasal atomization, has shown positive results in human medicine and in some animal species. The objective of this study was to evaluate the effects of intranasal atomization, compared to...

Mirra, A., Maidanskaia, E. G., Carmo, L. P. et al. 2023. How is depth of anaesthesia assessed in experimental pigs? A scoping review. PLOS ONE 18(3), e0283511.

Despite the large number of pigs involved in translational studies, no gold standard depth of anaesthesia indicators are available. We undertook a scoping review to investigate and summarize the evidence that sustains or contradicts the...

Ruvira, S., Rodríguez-Rodríguez, P., Cañas, S. et al. 2023. Evaluation of parameters which influence voluntary ingestion of supplements in rats. Animals 13(11), 1827.

Drug safety and efficacy studies frequently use oral gavage, but repetitive usage may cause problems. Administration through voluntary ingestion represents an opportunity for refinement. We aimed to develop a protocol for voluntary ingestion of gelatin-based...

Costea, R., Ene, I., Pavel, R. 2023. Pig sedation and anesthesia for medical research. Animals 13(24), 3807.

In clinical veterinary practice, proper training and expertise in anesthesia administration and monitoring are essential. Pigs are suitable experimental animals for many surgical techniques because they are similar in size to humans and have a...

Imboden, T. J., Pownall, W. R., Rubin, S. et al. 2023. Determination of a safe sedative combination of dexmedetomidine, ketamine and butorphanol for minor procedures in dogs by use of a stepwise optimization method. Acta Veterinaria Scandinavica 65(1), 41.

In veterinary practice, most minor procedures such as radiographs, skin biopsies, and wound treatments require sedation. The combination of butorphanol, ketamine, and dexmedetomidine is commonly used, but the ideal dosages for this combination have not...

Mirra, A., Hight, D., Kovacevic, A. et al. 2023. Sedline® miscalculation of depth of anaesthesia variables in two pigs due to electrocardiographic signal contamination. Animals 13(17), 2699.

Two young (11-week-old) pigs underwent sole propofol anaesthesia as part of an experimental study. The depth of anaesthesia was evaluated both clinically and using the electroencephalography(EEG)-based monitor Sedline; in particular, the patient state index, suppression...

Miguelena Chamorro, B., Swaminathan, G., Mundt, E. et al. 2023. Towards more translatable research: Exploring alternatives to gavage as the oral administration route of vaccines in rodents for improved animal welfare and human relevance. Lab Animal 52(9), 195–197.

Oral vaccines are gaining attention for their ease of administration and ability to activate mucosal immune responses. However, preclinical studies using this route often require the use of gavage, which has limitations. In this comment...

Leyden, C., Brüggemann, T., Debinski, F. et al. 2022. Efficacy of tricaine (MS-222) and hypothermia as anesthetic agents for blocking sensorimotor responses in larval zebrafish. Frontiers in Veterinary Science 9, 864573.

Tricaine, or MS-222, is the most commonly used chemical anesthetic in zebrafish research. It is thought to act via blocking voltage-gated sodium channels, though its mechanism of action, particularly at the neuronal level, is not...

Bartlett, J., Davies, J., Purawijaya, D. et al. 2022. Refinement of handling and dosing methods for rats and mice. Animal Technology and Welfare 21(2), 120-124.

Modified Handling for Mice: Handling mice by gripping the base of the tail has been shown to negatively impact animal welfare by increasing anxiety and aversion to handling. We aimed to refi ne the dosing...

Chesler, K. C., Motz, C. T., Bales, K. L. et al. 2022. Voluntary oral dosing for precise experimental compound delivery in adult rats. Laboratory Animals 56(2), 147-156.

Preclinical drug studies routinely administer experimental compounds to animal models with the goal of minimizing potential adverse events from the procedure. In this study, we assessed the ability to train adult male Long Evans rats...

Farag, A., Mandour, A. S., Hamabe, L. et al. 2022. Novel protocol to establish the myocardial infarction model in rats using a combination of medetomidine-midazolam-butorphanol (MMB) and atipamezole. Frontiers in Veterinary Science 9, 1064836.

Myocardial infarction (MI) is one of the most common cardiac problems causing deaths in humans. Previously validated anesthetic agents used in MI model establishment are currently controversial with severe restrictions because of ethical concerns. The...

Kulyar, M. F.-A., Ashfaq, K., Aqib, A. I. et al. 2022. Enhanced healing activity of manuka honey and nitrofurazone composite in full-thickness burn wounds in the rabbit model. Frontiers in Veterinary Science 9, 875629.

Burns cause many significant changes in metabolism and inflammatory reactions, leading to poor regeneration in animals and humans. A list of medicines to treat burns is available in the market. But due to the high...

Mason, G. J., Lavery, J. M. 2022. What is it like to be a bass? Red herrings, fish pain and the study of animal sentience. Frontiers in Veterinary Science 9, 788289.

Debates around fishes’ ability to feel pain concern sentience: do reactions to tissue damage indicate evaluative consciousness (conscious affect), or mere nociception? Thanks to Braithwaite’s research leadership, and concerns that current practices could compromise welfare...

Söbbeler, F. J., Wendt, S., Briese, A. et al. 2022. Comparative study of pain-related responses of male piglets up to seven days of age to the application of different local anaesthetics and subsequent castration. Animals 12(20), 2833.

To evaluate pain responses to intratesticular and subscrotal injection of three local anaesthetics and their efficacy during castration a randomized controlled study was conducted. In groups of 20 piglets, procaine (2%), lidocaine (2%), or mepivacaine...

Huss, M. K., Pacharinsak, C. 2022. A review of long-acting parenteral analgesics for mice and rats. JAALAS 61(6), 595–602.

Appropriate analgesia is a crucial part of rodent postoperative and postprocedural pain. Providing appropriate analgesia is an ethical obligation, a regulatory requirement, and an essential element of obtaining quality scientific results and conducting reproducible data...

Owen, J. P., Kelsh, R. N. 2021. A suitable anaesthetic protocol for metamorphic zebrafish. PLOS ONE 16(3), e0246504.

Zebrafish are frequently used as a means to investigate development. These studies increasingly require repeated anaesthesia of zebrafish during juvenile (i.e. metamorphic) stages. The effects of anaesthesia during this time remain poorly studied. The aim...

Stevens, C., Hawkins, P., Smulders, T. V. et al. 2021. Report of the 2020 RSPCA/UFAW rodent and rabbit welfare meeting. Animal Technology and Welfare 20(1), 21-33.

The RSPCA/UFAW rodent and rabbit welfare group has held a one-day meeting every autumn for the last 27 years, so that its members can discuss current welfare research, exchange views on welfare issues and share...

Manell, E., Hedenqvist, P., Jensen-Waern, M. 2021. Training pigs for oral glucose tolerance test—Six years’ experience of a refined model. Animals 11(6), 1677.

Animal models of human diseases are important in biomedical research. When using animals for scientific purposes, the 3Rs (replace, reduce, refine) should be considered. Refinement of animal models is essential to ensure best use of...

Chang, L.-J., Ko, J. C., Weil, A. B. et al. 2021. Comparison of anesthetic and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol, tiletamine-zolazepam-xylazine-butorphanol, and ketamine-detomidine-butorphanol in pigs. Journal of the AVMA 258(8), 883-891.

OBJECTIVE: To evaluate and compare the anesthetic, analgesic, and cardiorespiratory effects of tiletamine-zolazepam-detomidine-butorphanol (TZDB), tiletamine-zolazepam-xylazine-butorphanol (TZXB), and ketamine-detomidine-butorphanol (KDB) in pigs and to assess anesthetic recovery duration and quality following administration of tolazoline as a...

Satokar, V., Vickers, M., Bridge-Comer, P. et al. 2021. Emulsified gels: A refined vehicle for accurate and rapid oral administration of lipid based preparations to rats. Animal Technology and Welfare 20(2), 95-103.

Oro-gastric gavage is used to accurately administer nutritional substances or drugs to animals. However, it induces stress and has a substantial risk of mishap. Incorporation into edible gels is difficult for lipid-based preparations. We report...

Kinaci, A., Vaessen, K., Redegeld, S. et al. 2021. Minimizing complications in a porcine survival craniotomy model. Laboratory Animals 55(5), 435-442.

A large craniotomy survival porcine model is useful for scientific research. The surgical approaches and complications of craniotomies in pigs have not been published before. This study describes how large craniotomies were performed in 46...

Jorge, S., Ferreira, J. M., Olsson, I. A. S. et al. 2021. Efficacy and behavioral recovery of different anesthetics. Zebrafish 18(5), 330-337.

The use of proper anesthesia in zebrafish research is essential to ensure fish welfare and data reliability. However, anesthesia long-term side effects remain poorly understood. The purpose of this study was to assess anesthesia quality...

Lervik, A., Toverud, S. F., Krontveit, R. et al. 2020. A comparison of respiratory function in pigs anaesthetised by propofol or alfaxalone in combination with dexmedetomidine and ketamine. Acta Veterinaria Scandinavica 62(1), 1-9.

Background: General anaesthesia in pigs maintained with intravenous drugs such as propofol may cause respiratory depression. Alfaxalone gives less respiratory depression than propofol in some species. The aim of the investigation was to compare respiratory...